POSACONAZOLE CRESCENT

Treatment should be initiated by a physician experienced in the management of fungal infections or in the supportive care in the high-risk patients for which posaconazole is indicated as prophylaxis. Non-Interchangeability between posaconazole tablets and posaconazole oral suspension.

Posaconazole oral suspension is indicated for the adult population (≥18 years old) only. Another formulation (Posaconazole gastro-resistant powder and solvent for oral suspension) is available for paediatric patients from 2 years to less than 18 years of age.

The oral suspension are not to be used interchangeably due to the differences between these two formulations in frequency of dosing, administration with food and plasma drug concentration achieved. Therefore, follow the specific dosage recommendations for each formulation.

Posology Posaconazole is available in other forms and strengths, however not under this tradename. Posaconazole tablets are the preferred formulation to optimize plasma concentrations and generally provide higher plasma drug exposures than posaconazole oral suspension.

Recommended dose is shown in Table 1. 2) Refractory invasive fungal infections (IFI)/patients with IFI intolerant to 1st line therapy 200 mg (5 mL) four times a day. Alternatively, patients who can tolerate food or a nutritional supplement may take 400 mg (10 mL) twice a day during or immediately following a meal or nutritional supplement.

Duration of therapy should be based on the severity of the underlying disease, recovery from immunosuppression, and clinical response. 5 mL) once a day for 13 days. Each dose of posaconazole should be administered during or immediately after a meal, or a nutritional supplement in patients who cannot tolerate food to enhance the oral absorption and to ensure adequate exposure.

Prophylaxis of invasive fungal infections 200 mg (5 mL) three times a day. Each dose of posaconazole should be administered during or immediately after a meal, or a nutritional supplement in patients who cannot tolerate food to enhance the oral absorption and to ensure adequate exposure.

The duration of therapy is based on recovery from neutropenia or immunosuppression. For patients with acute myelogenous leukaemia or myelodysplastic syndromes, prophylaxis with posaconazole should start several days before the anticipated onset of neutropenia and continue for 7 days after the neutrophil count rises above 500 cells per mm3.

2). 2). It is recommended to exercise caution due to the potential for higher plasma exposure. 08 The safety and efficacy of posaconazole in children aged below 18 years have not been established in children and adolescents aged below 18 years.

2, but no recommendation on a posology can be made. Method of administration For oral use. The oral suspension must be shaken well before use.

Summary of the safety profile The safety of posaconazole oral suspension has been assessed in > 2,400 patients and healthy volunteers enrolled in clinical trials and from post-marketing experience. The most frequently reported serious related adverse reactions included nausea, vomiting, diarrhoea, pyrexia, and increased bilirubin.

Tabulated list of adverse reactions Within the organ system classes, adverse reactions are listed under headings of frequency using the following categories: very common (≥1/10); common (≥1/100 to <1/10); uncommon (≥1/1,000 to <1/100); rare (≥ 1/10,000 to <1/1,000); very rare (<1/10,000); not known (cannot be estimated from the available data).

08 System organ class Frequency Preferred Term Common Liver function tests raised (ALT increased, AST increased, bilirubin increased, alkaline phosphatase increased, GGT increased) Uncommon Hepatocellular damage, hepatitis, jaundice, hepatomegaly, cholestasis, hepatic toxicity, hepatic function abnormal Hepatobiliary disorders Rare Hepatic failure, hepatitis cholestatic, hepatosplenomegaly, liver tenderness, asterixis Common Rash, pruritis Uncommon Mouth ulceration, alopecia, dermatitis, erythema, petechiae Rare Stevens-Johnson syndrome, vesicular rash Skin and subcutaneous tissue disorders Not known photosensitivity reaction§ Musculoskeletal and connective tissue disorders Uncommon Back pain, neck pain, musculoskeletal pain, pain in extremity Uncommon Acute renal failure, renal failure, blood creatinine increased Renal and urinary disorders Rare Renal tubular acidosis, interstitial nephritis Uncommon Menstrual disorderReproductive system and breast disorders Rare Breast pain Common Pyrexia (fever), asthenia, fatigue Uncommon Oedema, pain, chills, malaise, chest discomfort, drug intolerance, feeling jittery, mucosal inflammation General disorders and administration site conditions Rare Tongue oedema, face oedema Investigations Uncommon Altered medicine levels, blood phosphorus decreased, chest x-ray abnormal *Based on adverse reactions observed with the oral suspension, gastro-resistant tablets, and concentrate for solution for infusion.

4. 4). Reporting of suspected adverse reactions Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store.

Hypersensitivity There is no information regarding cross-sensitivity between posaconazole and other azole antifungal agents. Caution should be used when prescribing posaconazole to patients with hypersensitivity to other azoles. g. mild to moderate elevations in ALT, AST, alkaline phosphatase, total bilirubin and/or clinical hepatitis) have been reported during treatment with posaconazole.

Elevated liver function tests were generally reversible on discontinuation of therapy and in some instances these tests normalised without interruption of therapy. Rarely, more severe hepatic reactions with fatal outcomes have been reported.

2). Monitoring of hepatic function Liver function tests should be evaluated at the start of and during the course of posaconazole therapy. 08 Patients who develop abnormal liver function tests during posaconazole therapy must be routinely monitored for the development of more severe hepatic injury.

Patient management should include laboratory evaluation of hepatic function (particularly liver function tests and bilirubin). Discontinuation of posaconazole should be considered if clinical signs and symptoms are consistent with development of liver disease.

QTc prolongation Some azoles have been associated with prolongation of the QTc interval. 5). 3). Electrolyte disturbances, especially those involving potassium, magnesium or calcium levels, should be monitored and corrected as necessary before and during posaconazole therapy.

5). g. midazolam, triazolam, alprazolam) should only be considered if clearly necessary. 5). VincristineToxicity Concomitant administration of azole antifungals, including posaconazole, with vincristine has been associated with neurotoxicity and other serious adverse reactions, including seizures, peripheral neuropathy, syndrome of inappropriate antidiuretic hormone secretion, and paralytic ileus.

5). 5). Refer to the venetoclax SmPC for detailed guidance. 5). Gastrointestinal dysfunction There are limited pharmacokinetic data in patients with severe gastrointestinal dysfunction (such as severe diarrhoea). Patients who have severe diarrhoea or vomiting should be monitored closely for breakthrough fungal infections.

Photosensitivity reaction Posaconazole may cause increased risk of photosensitivity reaction. Patients should be advised to avoid sun exposure during treatment without adequate protection such as protective clothing and sunscreen with a high sun protection factor (SPF).

11 g of glucose per 5 ml of suspension. This should be taken into account in patients with diabetes mellitus. Patients with rare glucose-galactose malabsorption should not take this medicine. May be harmful to the teeth. Sodium This medicine contains less than 1 mmol sodium (23 mg) per 5 ml of suspension, that is to say essentially ‘sodium-free’.

Sodium benzoate (E211) This medicinal product contains 10 mg of sodium benzoate (E211) per 5 mL of suspension.

1. 5). 5). 5). 5).